This is an interdisciplinary program to explore the integrated function of respiration and circulation at different levels of interaction. We attempt to show how mechanical stresses between lung tissue and pulmonary vessels influence pulmonary hemodynamics and pulmonary fluid exchange. Similarly, we explore how the mechanical stresses between the lungs, thorax, and heart influence both right and left ventricular performance and afterload. The mechanical interdependence between the lungs, pulmonary vessels, and heart plays a major role in the effect of spontaneous and artificial ventilation in the production and therapy of pulmonary edema. We have developed a number of special animal preparations to explore the possibility that the transport of oxygen between air and blood and between blood and tissue might involve facilitative diffusion through cytochrome P-450. We are examining the physiological effects of hypoxia, hypercapnia, and acidosis on the carotid and aortic bodies, the pulmonary and cerebral circulation, and cardiac and skeletal muscle. We are studying an evaluation of oxygenases such as cytochrome P-450 acting as the oxygen sensor responsible for hypoxic pulmonary vasoconstriction. We are studying the effect of intracellular concentrations of hydrogen ion, high energy phosphates, and cAMP and the chemical and electrophysiological events involved in excitation-contraction coupling in a vascularly perfused isolated rat diaphragm preparation. The special circulatory and respiratory experimental preparations are being used to determine how immunological factors produce anaphylaxis and the optimal therapy for it.